{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:08:49Z","timestamp":1792786129634,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T00:00:00Z","timestamp":1558051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"SenzaGen AB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Proactive identification of chemicals with skin sensitizing properties is a key toxicological endpoint within chemical safety assessment, as required by legislation for registration of chemicals. In order to meet demands of increased animal welfare and facilitate increased testing efficiency also in nonregulatory settings, considerable efforts have been made to develop nonanimal approaches to replace current animal testing. Genomic Allergen Rapid Detection (GARD\u2122) is a state-of-the-art technology platform, the most advanced application of which is the assay for assessment of skin sensitizing chemicals, GARD\u2122skin. The methodology is based on a dendritic cell (DC)-like cell line, thus mimicking the mechanistic events leading to initiation and modulation of downstream immunological responses. Induced transcriptional changes are measured following exposure to test chemicals, providing a detailed evaluation of cell activation. These changes are associated with the immunological decision-making role of DCs in vivo and include among other phenotypic modifications, up-regulation of co-stimulatory molecules, induction of cellular and oxidative stress pathways and xenobiotic responses, and provide a holistic readout of substance-induced DC activation. Here, results from an inter-laboratory ring trial of GARD\u2122skin, conducted in compliance with OECD guidance documents and comprising a blinded chemical test set of 28 chemicals, are summarized. The assay was found to be transferable to na\u00efve laboratories, with an inter-laboratory reproducibility of 92.0%. The within-laboratory reproducibility ranged between 82.1% and 88.9%, whereas the cumulative predictive accuracy across the 3 laboratories was 93.8%. It was concluded that GARD\u2122skin is a robust and reliable method for the identification of skin sensitizing chemicals and suitable for stand-alone use or as a constituent of integrated testing. These data form the basis for the regulatory validation of GARD\u2122skin.<\/jats:p>","DOI":"10.1093\/toxsci\/kfz108","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T19:21:00Z","timestamp":1557256860000},"page":"374-381","source":"Crossref","is-referenced-by-count":44,"title":["Validation of the GARD\u2122skin Assay for Assessment of Chemical Skin Sensitizers: Ring Trial Results of Predictive Performance and Reproducibility"],"prefix":"10.1093","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9506-0078","authenticated-orcid":false,"given":"Henrik","family":"Johansson","sequence":"first","affiliation":[{"name":"SenzaGen AB, 22381 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3339-1269","authenticated-orcid":false,"given":"Robin","family":"Gradin","sequence":"additional","affiliation":[{"name":"SenzaGen AB, 22381 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Johansson","sequence":"additional","affiliation":[{"name":"SenzaGen AB, 22381 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Els","family":"Adriaens","sequence":"additional","affiliation":[{"name":"Adriaens Consulting BVBA, Aalter 9881, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Edwards","sequence":"additional","affiliation":[{"name":"Burleson Research Technologies, Morrisville, North Carolina 27560"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Zuckerst\u00e4tter","sequence":"additional","affiliation":[{"name":"Eurofins BioPharma Product Testing Munich GmbH, 82152 Planegg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Jerre","sequence":"additional","affiliation":[{"name":"SenzaGen AB, 22381 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Burleson","sequence":"additional","affiliation":[{"name":"Burleson Research Technologies, Morrisville, North Carolina 27560"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Gehrke","sequence":"additional","affiliation":[{"name":"Eurofins BioPharma Product Testing Munich GmbH, 82152 Planegg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin L","family":"Roggen","sequence":"additional","affiliation":[{"name":"3RsMC Aps, 2800 Lyngby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,17]]},"reference":[{"key":"2019072509002301400_kfz108-B1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s00204-011-0693-2","article-title":"Alternative (non-animal) methods for cosmetics testing: Current status and future prospects-2010","volume":"85","author":"Adler","year":"2011","journal-title":"Arch. Toxicol."},{"key":"2019072509002301400_kfz108-B2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3109\/1547691X.2012.711782","article-title":"Danger, intracellular signaling, and the orchestration of dendritic cell function in skin sensitization","volume":"10","author":"Ainscough","year":"2013","journal-title":"J. Immunotoxicol."},{"key":"2019072509002301400_kfz108-B3","doi-asserted-by":"crossref","DOI":"10.1186\/2050-6511-15-5","article-title":"Skin sensitizers differentially regulate signaling pathways in MUTZ-3 cells in relation to their individual potency","volume":"15","author":"Albrekt","year":"2014","journal-title":"BMC Pharmacol. Toxicol."},{"key":"2019072509002301400_kfz108-B4","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.tiv.2005.10.012","article-title":"Development of an in vitro skin sensitization test using human cell lines: The human cell line activation test (h-CLAT). I. Optimization of the h-CLAT protocol","volume":"20","author":"Ashikaga","year":"2006","journal-title":"Toxicol. In Vitro"},{"key":"2019072509002301400_kfz108-B5","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s00204-017-2097-4","article-title":"Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: Position of the International Cooperation on Alternative Test Methods","volume":"92","author":"Casati","year":"2018","journal-title":"Arch. Toxicol."},{"key":"2019072509002301400_kfz108-B6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/BF00994018","article-title":"Support-vector networks","volume":"20","author":"Cortes","year":"1995","journal-title":"Mach. 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Toxicol."},{"key":"2019072509002301400_kfz108-B11","doi-asserted-by":"crossref","first-page":"379.","DOI":"10.1186\/1471-2164-15-379","article-title":"Evaluation of high throughput gene expression platforms using a genomic biomarker signature for prediction of skin sensitization","volume":"15","author":"Forreryd","year":"2014","journal-title":"BMC Genomics"},{"key":"2019072509002301400_kfz108-B12","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.tiv.2016.09.013","article-title":"From genome-wide arrays to tailor-made biomarker readout - Progress towards routine analysis of skin sensitizing chemicals with GARD\u2122","volume":"37","author":"Forreryd","year":"2016","journal-title":"Toxicol. 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Sci."},{"key":"2019072509002301400_kfz108-B20","first-page":"515","article-title":"Evaluation of the GARD\u2122 assay in a blind Cosmetics Europe study","volume":"34","author":"Johansson","year":"2017","journal-title":"Altex"},{"key":"2019072509002301400_kfz108-B21","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2164-12-399","article-title":"A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests","volume":"12","author":"Johansson","year":"2011","journal-title":"BMC Genomics"},{"key":"2019072509002301400_kfz108-B22","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/toxsci\/kfu046","article-title":"Genomic allergen rapid detection in-house validation \u2013 A proof of concept","volume":"139","author":"Johansson","year":"2014","journal-title":"Toxicol. 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Invest Dermatol."},{"key":"2019072509002301400_kfz108-B27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/cod.12311","article-title":"New concepts in cutaneous allergy","volume":"72","author":"Martin","year":"2015","journal-title":"Contact Dermatitis"},{"key":"2019072509002301400_kfz108-B28","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1111\/j.1398-9995.2011.02652.x","article-title":"Mechanisms of chemical-induced innate immunity in allergic contact dermatitis","volume":"66","author":"Martin","year":"2011","journal-title":"Allergy"},{"key":"2019072509002301400_kfz108-B29","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1093\/toxsci\/kfp228","article-title":"The Nrf2-Keap1-ARE toxicity pathway as a cellular sensor for skin sensitizers\u2013functional relevance and a hypothesis on innate reactions to skin sensitizers","volume":"113","author":"Natsch","year":"2010","journal-title":"Toxicol. 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Toxicol."},{"key":"2019072509002301400_kfz108-B31","volume-title":"Test No. 406: Skin Sensitization, OECD Guidelines for the Testing of Chemicals, Section 4","author":"OECD","year":"1992"},{"key":"2019072509002301400_kfz108-B32","volume-title":"Series on Testing and Assessment, No 34: Guidance Document on the Validation and International Acceptance of New or Updated Test Methods for Hazard Assessment","author":"OECD","year":"2005"},{"key":"2019072509002301400_kfz108-B33","volume-title":"Series on Testing and Assessment, No 1: Guidance Document for the Development of OECD Guidelines for Testing of Chemicals (as Revised in 2009","author":"OECD","year":"2009"},{"key":"2019072509002301400_kfz108-B34","volume-title":"Test No. 429: Skin Sensitization: Local Lymph Node Assay, OECD Guidelines for the Testing of Chemicals, Section 4","author":"OECD","year":"2010"},{"key":"2019072509002301400_kfz108-B35","doi-asserted-by":"crossref","DOI":"10.1787\/9789264221444-en","volume-title":"The Adverse Outcome Pathway for Skin Sensitization Initiated by Covalent Binding to Proteins OECD Series on Testing and Assessment, No. 168","author":"OECD","year":"2014"},{"key":"2019072509002301400_kfz108-B36","volume-title":"Test No. 442C: In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA), OECD Guidelines of the Testing of Chemicals, Section 4","author":"OECD","year":"2015"},{"key":"2019072509002301400_kfz108-B37","volume-title":"Series on Testing and Assessment, No 256: Guidance Document on the Reporting of Defined Approaches and Individual Information Sources to Be Used within Integrated Approaches to Testing and Assessment (IATA) for Skin Sensitisation, Annex 1, Annex 2","author":"OECD","year":"2016"},{"key":"2019072509002301400_kfz108-B38","volume-title":"Test No. 442D: In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method, OECD Guidelines of the Testing of Chemicals, Section 4","author":"OECD","year":"2018"},{"key":"2019072509002301400_kfz108-B39","doi-asserted-by":"crossref","DOI":"10.1787\/9789264264359-en","volume-title":"Test No. 442E: In Vitro Skin Sensitisation: In Vitro Skin Sensitisation Assays Addressing the Key Event on Activation of Dendritic Cells on the Adverse Outcome Pathway for Skin Sensitisation, OECD Guidelines for the Testing of Chemicals, Section 4","author":"OECD","year":"2018"},{"key":"2019072509002301400_kfz108-B40","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.yrtph.2018.07.014","article-title":"Is a combination of assays really needed for non-animal prediction of skin sensitization potential? Performance of the GARD\u2122 (Genomic Allergen Rapid Detection) assay in comparison with OECD guideline assays alone and in combination","volume":"98","author":"Roberts","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"2019072509002301400_kfz108-B41","year":"2009"},{"key":"2019072509002301400_kfz108-B42","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.yrtph.2014.12.008","article-title":"Assessing skin sensitization hazard in mice and men using non-animal test methods","volume":"71","author":"Urbisch","year":"2015","journal-title":"Regul. Toxicol. Pharmacol."}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfz108\/28834787\/kfz108.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/170\/2\/374\/28998950\/kfz108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T14:46:14Z","timestamp":1721227574000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/170\/2\/374\/5490849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,17]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,5,17]]},"published-print":{"date-parts":[[2019,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfz108","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,8]]},"published":{"date-parts":[[2019,5,17]]}}}